Cardiovascular disease is a leading cause of death in the developed world. Patients having such disease usually have narrowing or closing (stenosis) in one or more arteries. The use of stents in the treatment of cardiovascular disease is well known. Stents are typically delivered in a contracted state to the treatment area within a lumen, where they are then expanded. Balloon-expandable stents expand from a contracted state by deforming in response to a force exerted upon the stent body by a balloon that is inflated within the stent's lumen. Once expanded within a body lumen, the stent body is strong enough to resist any contracting force exerted by the body lumen wall so that the stent maintains its expanded diameter. In contrast, self-expanding stents have resilient bodies that exert a radial expansion force when the stent is compressed. A self-expanding stent that is deployed within a body lumen will expand until the body lumen wall exerts a compressive force against the stent that is equal to the radial expansion force.
The use of balloon-expandable and self-expanding stents, however, may have the disadvantage of causing additional trauma to a body lumen upon deployment of the stent. Typically, a stent is expanded within a body lumen so that the diameter of the stent is greater than that of the body lumen. As a result, the edges of the ends of stent may be pressed into the wall of body lumen, stressing the wall to the point of creating additional trauma, i.e., cutting or tearing of the body lumen wall. This trauma may ultimately lead to restenosis (re-narrowing) in the areas of the body lumen adjacent the ends of the stent.
Recently, various types of drug-coated stents have been used for the localized delivery of drugs to the wall of a body lumen to further prevent restenosis. However, the hydrophobic or hydrophilic nature of drugs that are used in the coating can impose a number of difficulties on the design of drug delivery coating. For example, with respect to the delivery of a hydrophobic drug like paclitaxel, which is the active ingredient of Taxol®, the hydrophobic drug will tend to cluster inside a hydrophilic coating and as a result, will not be evenly distributed throughout the coating. On the other hand, when using a hydrophobic matrix that allows an even distribution of the hydrophobic drug, it is difficult to get a 100% release of the hydrophobic drug into a hydrophilic environment as the hydrophobic drug will be more inclined to remain inside the hydrophobic matrix environment.
Similarly, when using a block-polymer with both hydrophobic and hydrophilic side-branches, one will get a self-assembly of the alike structures whereby the hydrophobic drug will be attached to the regions of the highest hydrophobicity and therefore, making it difficult to release the hydrophobic drug in an effective and consistent manner. Similarly, a hydrophilic drug will be attached to the region of highest hydrophilicity, thereby making effective and consistent release of the drug difficult.
The use of biodegradable coatings has also been proposed as a possible solution to release the hydrophobic drug into a hydrophilic environment because of the erosion or degradation of the surrounding matrix. However, as in the case of using a hydrophobic matrix, it is difficult to obtain a steady and complete release of the hydrophobic drug because the hydrophobic drug will be more inclined to stay in the remaining hydrophobic coating even as the hydrophobic coating degrades. The delivery of a hydrophilic drug to an environment that is hydrophobic or less hydrophilic relative to the hydrophilic drug may be equally challenging.
In order to optimize drug delivery, one has to solve the contradiction of a hydrophobic drug that needs to act as hydrophilic or vice versa.